The mouse is the most commonly used animal in biomedical research comprising >90% of all animal experimentation. This mammalian species is often the prime choice to flesh out mechanisms of action of drugs and to establish biochemical signaling pathways prior to entering human trials. Directly relevant to PENTACON, mice were used to predict and then assign mechanistic understanding to all recognized features thrombosis, hypertension, heart failure, dysrhythmia of the cardiovascular hazard in humans taking COX-2 selective NSAIDs (1,2). More than 20 genetic mouse models that disrupt or perturb the COX biosyntheticresponse pathway have been developed by PENTACON members, a unique resource for use in this proposal.